{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:18:08Z","timestamp":1792113488085,"version":"4.4.0"},"reference-count":47,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T00:00:00Z","timestamp":1669507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82001188"],"award-info":[{"award-number":["82001188"]}]},{"name":"National Natural Science Foundation of China","award":["JCYJ20190807154401665"],"award-info":[{"award-number":["JCYJ20190807154401665"]}]},{"name":"National Natural Science Foundation of China","award":["JCYJ20180305163652073"],"award-info":[{"award-number":["JCYJ20180305163652073"]}]},{"name":"National Natural Science Foundation of China","award":["SZXK044"],"award-info":[{"award-number":["SZXK044"]}]},{"name":"National Natural Science Foundation of China","award":["SZSM202011021"],"award-info":[{"award-number":["SZSM202011021"]}]},{"name":"Science and Technology Planning Project of Shenzhen","award":["82001188"],"award-info":[{"award-number":["82001188"]}]},{"name":"Science and Technology Planning Project of Shenzhen","award":["JCYJ20190807154401665"],"award-info":[{"award-number":["JCYJ20190807154401665"]}]},{"name":"Science and Technology Planning Project of Shenzhen","award":["JCYJ20180305163652073"],"award-info":[{"award-number":["JCYJ20180305163652073"]}]},{"name":"Science and Technology Planning Project of Shenzhen","award":["SZXK044"],"award-info":[{"award-number":["SZXK044"]}]},{"name":"Science and Technology Planning Project of Shenzhen","award":["SZSM202011021"],"award-info":[{"award-number":["SZSM202011021"]}]},{"name":"Shenzhen Key Medical Discipline Construction Fund","award":["82001188"],"award-info":[{"award-number":["82001188"]}]},{"name":"Shenzhen Key Medical Discipline Construction Fund","award":["JCYJ20190807154401665"],"award-info":[{"award-number":["JCYJ20190807154401665"]}]},{"name":"Shenzhen Key Medical Discipline Construction Fund","award":["JCYJ20180305163652073"],"award-info":[{"award-number":["JCYJ20180305163652073"]}]},{"name":"Shenzhen Key Medical Discipline Construction Fund","award":["SZXK044"],"award-info":[{"award-number":["SZXK044"]}]},{"name":"Shenzhen Key Medical Discipline Construction Fund","award":["SZSM202011021"],"award-info":[{"award-number":["SZSM202011021"]}]},{"name":"Sanming Project of Medicine in Shenzhen","award":["82001188"],"award-info":[{"award-number":["82001188"]}]},{"name":"Sanming Project of Medicine in Shenzhen","award":["JCYJ20190807154401665"],"award-info":[{"award-number":["JCYJ20190807154401665"]}]},{"name":"Sanming Project of Medicine in Shenzhen","award":["JCYJ20180305163652073"],"award-info":[{"award-number":["JCYJ20180305163652073"]}]},{"name":"Sanming Project of Medicine in Shenzhen","award":["SZXK044"],"award-info":[{"award-number":["SZXK044"]}]},{"name":"Sanming Project of Medicine in Shenzhen","award":["SZSM202011021"],"award-info":[{"award-number":["SZSM202011021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuropathic pain is a refractory chronic disease affecting millions of people worldwide. Given that present painkillers have poor efficacy or severe side effects, developing novel analgesics is badly needed. The multiplex structure of active ingredients isolated from natural products provides a new source for phytochemical compound synthesis. Here, we identified a natural product, Narirutin, a flavonoid compound isolated from the Citrus unshiu, showing antinociceptive effects in rodent models of neuropathic pain. Using calcium imaging, whole-cell electrophysiology, western blotting, and immunofluorescence, we uncovered a molecular target for Narirutin\u2019s antinociceptive actions. We found that Narirutin (i) inhibits Veratridine-triggered nociceptor activities in L4-L6 rat dorsal root ganglion (DRG) neurons, (ii) blocks voltage-gated sodium (NaV) channels subtype 1.7 in both small-diameter DRG nociceptive neurons and human embryonic kidney (HEK) 293 cell line, (iii) does not affect tetrodotoxin-resistant (TTX-R) NaV channels, and (iv) blunts the upregulation of Nav1.7 in calcitonin gene-related peptide (CGRP)-labeled DRG sensory neurons after spared nerve injury (SNI) surgery. Identifying Nav1.7 as a molecular target of Narirutin may further clarify the analgesic mechanism of natural flavonoid compounds and provide an optimal idea to produce novel selective and efficient analgesic drugs.<\/jats:p>","DOI":"10.3390\/ijms232314842","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T04:58:50Z","timestamp":1669784330000},"page":"14842","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Reversal of Peripheral Neuropathic Pain by the Small-Molecule Natural Product Narirutin via Block of Nav1.7 Voltage-Gated Sodium Channel"],"prefix":"10.3390","volume":"23","author":[{"given":"Haoyi","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Anatomy and Histology, Shenzhen University Health Science Center, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4575-3933","authenticated-orcid":false,"given":"Zhiming","family":"Shan","sequence":"additional","affiliation":[{"name":"Laboratory and Clinical Research Institute for Pain, Department of Anaesthesiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China"},{"name":"Department of Anesthesiology, Shenzhen People\u2019s Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen 518020, China"},{"name":"Shenzhen Engineering Research Center of Anesthesiology, Shenzhen 518020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, Shenzhen University Health Science Center, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, Shenzhen University Health Science Center, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxian","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, Shenzhen University Health Science Center, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, Shenzhen University Health Science Center, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaojie","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, Shenzhen University Health Science Center, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Aijia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, City University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi Wai","family":"Cheung","sequence":"additional","affiliation":[{"name":"Laboratory and Clinical Research Institute for Pain, Department of Anaesthesiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1482-1291","authenticated-orcid":false,"given":"Song","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, Shenzhen University Health Science Center, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1016\/j.pain.2011.06.017","article-title":"A new definition of neuropathic pain","volume":"152","author":"Jensen","year":"2011","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1001\/jama.2018.0899","article-title":"Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients with Chronic Back Pain or Hip or Knee Osteoarthritis Pain: The SPACE Randomized Clinical Trial","volume":"319","author":"Krebs","year":"2018","journal-title":"JAMA"},{"key":"ref_3","first-page":"CD011117","article-title":"Opioid agonist treatment for people who are dependent on pharmaceutical opioids","volume":"9","author":"Nielsen","year":"2022","journal-title":"Cochrane Database Syst. 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